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The AA profile of MP affects mammary gland metabolism and milk N efficiency of dairy cattle. Further, the frequency of dietary protein supplementation may influence N partitioning leading to reduced N excretion. This study investigated the effect of source and frequency of rumen-protected (RP) protein supplementation on apparent total-tract digestibility, milk production, mammary gland AA metabolism, and N balance of dairy cattle. Twenty-eight Holstein-Friesian cows (2.3 ± 0.9 lactations; 93 ± 27 d in milk; mean ± SD) were used in a randomized complete block design and fed a basal total mixed ration (TMR) consisting of 41% corn silage, 32% grass silage, and 27% concentrate (DM basis) and formulated to meet 100 and 95% of net energy and MP requirements, respectively. Cows were adapted to the basal TMR in a free stall barn for 7 d, moved to individual tie stalls for 13 d of adaptation to dietary treatments, and then moved into climate respiration chambers for a 4-d measurement period. Treatments consisted of the basal TMR (CON; 159 g CP/kg DM) or the basal TMR including 1 of 3 iso-MP supplements: 1) 315-g mixture of RP soybean meal and RP rapeseed meal fed daily (ST-RPSR), 2) 384-g mixture of RP His, RP Lys, and RP Met fed daily (ST-RPAA), and 3) 768-g mixture of RP His, RP Lys, and RP Met fed every-other day (OS-RPAA). The basal TMR with the addition of treatment supplements was designed to deliver 100% of required MP over a 48-h period. The mixture of His, Lys, and Met was formulated to deliver digestible AA in amounts relative to their concentration in casein. Compared with ST-RPSR, ST-RPAA increased milk protein and fat concentration, increased the arterial concentration of total His, Lys, and Met (HLM), decreased mammary clearance of HLM, and increased clearance of Phe, Leu and Tyr (tendency for Leu and Tyr). Rumen-protected protein source did not affect N balance, but the marginal use efficiency (efficiency of transfer of RP protein supplement into milk protein) of ST-RPAA (67%) was higher than that of ST-RPSR (17%). Milk protein concentration decreased with OS-RPAA compared with ST-RPAA. Arterial concentration of HLM increased on the non-supplemented day compared with the supplemented day with OS-RPAA, and there was no difference in arterial HLM concentration across days with ST-RPAA. Mammary uptake of HLM tended to increase on the non-supplemented day compared with the supplemented day with OS-RPAA. Supplementation frequency of RP AA did not affect N balance or overall milk N efficiency, but the marginal use efficiency of OS-RPAA (49%) was lower compared with ST-RPAA. Overall, mammary glands responded to an increased supply of His, Lys, and Met by reducing efflux of other EAA when RP His, RP Lys, and RP Met were supplemented compared with RP plant proteins. Mammary glands increased sequestration of EAA (primarily HLM) on the non-supplemented day with OS-RPAA, but supplementing RP AA according to a 24-h oscillating pattern did not increase N efficiency over static supplementation.
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BACKGROUND: Self-stigma is highly prevalent in serious mental illness (SMI) and is associated with poorer clinical and functional outcomes. Narrative enhancement and cognitive therapy (NECT) is a group-based intervention combining psychoeducation, cognitive restructuring and story-telling exercises to reduce self-stigma and its impact on recovery-related outcomes. Despite evidence of its effectiveness on self-stigma in schizophrenia-related disorders, it is unclear whether NECT can impact social functioning. METHODS: This is a 12-centre stepped-wedge cluster randomized controlled trial of NECT effectiveness on social functioning in SMI, compared to treatment as usual. One hundred and twenty participants diagnosed with schizophrenia, bipolar disorder or borderline personality disorder will be recruited across the 12 sites. The 12 centres participating to the study will be randomized into two groups: one group (group 1) receiving the intervention at the beginning of the study (T0) and one group (group 2) being a control group for the first 6 months and receiving the intervention after (T1). Outcomes will be compared in both groups at T0 and T1, and 6-month and 12-month outcomes for groups 1 and 2 will be measured without a control group at T2 (to evaluate the stability of the effects over time). Evaluations will be conducted by assessors blind to treatment allocation. The primary outcome is personal and social performance compared across randomization groups. Secondary outcomes include self-stigma, self-esteem, wellbeing, quality of life, illness severity, depressive symptoms and personal recovery. DISCUSSION: NECT is a promising intervention for reducing self-stigma and improving recovery-related outcomes in SMI. If shown to be effective in this trial, it is likely that NECT will be implemented in psychiatric rehabilitation services with subsequent implications for routine clinical practice. TRIAL REGISTRATION: ClinicalTrials.gov NCT03972735 . Trial registration date 31 May 2019.
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Terapia Cognitivo-Comportamental , Qualidade de Vida , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Interação Social , Estigma Social , Resultado do TratamentoRESUMO
INTRODUCTION: Every day, large numbers of patients benefit from effective transfusion substitution therapy, through transfusion procedures that are generally safe and reliable. This care practice is complex, due to its history through the ages, ethical aspects linked to the donation of blood from one human to another, and the procedures and protocols linked to it. Nurses are a key link in the transfusion chain and are directly affected by the procedures implemented to limit transfusion risks. In this research study, we studied the nurses' and midwives' representations of transfusion, to evaluate their possible effects on transfusion practices. METHODOLOGY: With the aid of the various actors involved in transfusion, we developed and tested a questionnaire, which was then sent to 690 professionals in 69 care units. RESULTS: In total, 491 questionnaires were analyzed, corresponding to a response rate of 71%. The data collected revealed a strong feeling of responsibility among the healthcare staff questioned, with great attention paid to transfusion safety. The risk to the patient is very much taken into account by these professionals, who consider transfusion to be a healthcare practice unlike any other, generating a certain stress that affected all those questioned, regardless of the number of years they had been in practice, but was tempered by knowledge. CONCLUSION: This survey shows that nurses and midwives are very aware of the risks of transfusion to the patient, and that they take these risks into account with the same diligence throughout their careers. It would be useful to carry out semi-directed interviews to refine some of these results further.
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Tocologia , Enfermeiras e Enfermeiros , Transfusão de Sangue , Feminino , Hospitais Universitários , Humanos , Gravidez , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Primary cutaneous CD8+ aggressive, epidermotropic, cytotoxic T-cell lymphoma is a rare disease with a poor prognosis. Herein we report a new case, with facial lesions, which was difficult to diagnose. PATIENTS AND METHODS: A 39-year-old woman was hospitalized for ulcerated nodules on the face that had been developing rapidly for 8 weeks. She had visited Djerba, Tunisia, 3 months earlier. No abnormalities were found on previous routine blood tests. Histopathological analysis of a skin biopsy had revealed non-specific lymphocytic infiltrate. Various therapies, including amoxicillin/clavulanic acid, valaciclovir, corticosteroids, colchicine and doxycycline, proved ineffective. Screening of the cutaneous sample for leishmaniasis proved positive using PCR but negative by direct examination and culture. Treatment was initiated with meglumine antimoniate. A further cutaneous biopsy revealed diffuse lymphocytic proliferation and led to a diagnosis of cutaneous CD8+ aggressive, epidermotropic, cytotoxic T-cell lymphoma. A PET scan showed multiple sites of hypermetabolism affecting the face and lymph nodes. Meglumine antimoniate was stopped and the patient experienced complete remission after chemotherapy. CONCLUSION: Ulcerated nodules with acute progression on acral sites are characteristic of cutaneous CD8+ aggressive, epidermotropic, cytotoxic T-cell lymphoma. In our case, the positive result of PCR screening for Leishmania that was ultimately considered a false positive was a confounding factor in the diagnostic process. Regarding therapy, aggressive treatment strategies such as multiagent chemotherapy and hematopoietic stem-cell transplantation are needed due to the rapid progression of the lymphoma.
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Linfoma Cutâneo de Células T , Neoplasias Cutâneas , Adulto , Linfócitos T CD8-Positivos , Feminino , Humanos , Linfonodos , Linfoma Cutâneo de Células T/diagnóstico , Linfoma Cutâneo de Células T/tratamento farmacológico , Pele , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/tratamento farmacológicoRESUMO
Bisphosphorylallenes were easily obtained in multigram scale from the Wittig-type rearrangement of bispropargyl alcohols. Unlike other conjugated bis-allenes, these reagents underwent a double cyclization mediated by iodine or copper dibromide leading to the formation of bis-1,2-oxaphospholenes.
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INTRODUCTION: The Merck Adenovirus-5 Gag/Pol/Nef HIV-1 subtype-B vaccine evaluated in predominately subtype B epidemic regions (Step Study), while not preventing infection, exerted vaccine-induced immune pressure on HIV-1 breakthrough infections. Here we investigated if the same vaccine exerted immune pressure when tested in the Phambili Phase 2b study in a subtype C epidemic. MATERIALS AND METHODS: A sieve analysis, which compares breakthrough viruses from placebo and vaccine arms, was performed on 277 near full-length genomes generated from 23 vaccine and 20 placebo recipients. Vaccine coverage was estimated by computing the percentage of 9-mers that were exact matches to the vaccine insert. RESULTS: There was significantly greater protein distances from the vaccine immunogen sequence in Gag (p=0.045) and Nef (p=0.021) in viruses infecting vaccine recipients compared to placebo recipients. Twenty-seven putative sites of vaccine-induced pressure were identified (p<0.05) in Gag (n=10), Pol (n=7) and Nef (n=10), although they did not remain significant after adjustment for multiple comparisons. We found the epitope sieve effect in Step was driven by HLA A∗02:01; an allele which was found in low frequency in Phambili participants compared to Step participants. Furthermore, the coverage of the vaccine against subtype C Phambili viruses was 31%, 46% and 14% for Gag, Pol and Nef, respectively, compared to subtype B Step virus coverage of 56%, 61% and 26%, respectively. DISCUSSION: This study presents evidence of sieve effects in Gag and Nef; however could not confirm effects on specific amino acid sites. We propose that this weaker signal of vaccine immune pressure detected in the Phambili study compared to the Step study may have been influenced by differences in host genetics (HLA allele frequency) and reduced impact of vaccine-induced immune responses due to mismatch between the viral subtype in the vaccine and infecting subtypes.
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Vacinas contra a AIDS/imunologia , Infecções por HIV/prevenção & controle , HIV-1/imunologia , Imunidade Ativa , Produtos do Gene gag do Vírus da Imunodeficiência Humana/imunologia , Produtos do Gene nef do Vírus da Imunodeficiência Humana/imunologia , Vacinas contra a AIDS/administração & dosagem , Adenoviridae , Estudos de Coortes , Método Duplo-Cego , Epitopos/genética , Epitopos/imunologia , Feminino , Frequência do Gene , Antígeno HLA-A2/genética , Antígeno HLA-A2/imunologia , Humanos , Masculino , Tamanho da Amostra , Cobertura Vacinal , Vacinas Sintéticas/administração & dosagem , Vacinas Sintéticas/imunologia , Produtos do Gene gag do Vírus da Imunodeficiência Humana/genética , Produtos do Gene nef do Vírus da Imunodeficiência Humana/genética , Produtos do Gene pol do Vírus da Imunodeficiência Humana/genética , Produtos do Gene pol do Vírus da Imunodeficiência Humana/imunologiaRESUMO
Striatal dopaminergic denervation leads to a change in afferent activity within the basal ganglia. Coupled with the effect of local dopaminergic denervation in the subthalamic nucleus, this is likely to affect the responsiveness of subthalamic neurons to their hyperdirect inputs in Parkinson's disease. Therefore, in this report, we investigated subthalamic nucleus responses to visual stimuli relayed by one such input - the superior colliculus - in 6-hydroxydopamine (6-OHDA)-lesioned rats. We used a protocol where the superior colliculus was selectively unlocked from the inhibitory effect of anesthesia with an injection of bicuculline, attenuating GABAergic inhibition in the colliculus, which arises predominantly from the substantia nigra pars reticulata. We found that visual responses in the superior colliculus were facilitated by partial or total lesions of dopaminergic neurons in the substantia nigra pars compacta, once the colliculus was disinhibited by bicuculline. Responses were faster, larger in amplitude and lasted longer compared to those in control rats. In the subthalamic nucleus, visual responses were also increased in amplitude and magnitude in partial or total lesioned groups. A classic hypothesis in Parkinson's disease suggests that following dopaminergic denervation, the discharge of cells in the substantia nigra pars reticulata increases, thereby intensifying the inhibitory influence that this structure exerts on its targets in the thalamus and brainstem. Our results suggest that neuroadaptations may have taken place within the superior colliculus in order to maintain normal function in the face of increased inhibitory tone coming from the substantia nigra pars reticulata, which once reduced, gave rise to facilitated responding. This facilitated responding in the superior colliculus then appears to lead to facilitated responding in the subthalamic nucleus.
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Adaptação Fisiológica/fisiologia , Transtornos Parkinsonianos/fisiopatologia , Núcleo Subtalâmico/fisiopatologia , Colículos Superiores/fisiopatologia , Percepção Visual/fisiologia , Animais , Modelos Animais de Doenças , Fenômenos Eletrofisiológicos , Imuno-Histoquímica , Masculino , Ratos , Ratos Long-EvansRESUMO
STUDY QUESTION: Are temporal trends and values of semen quality parameters in France identifiable in partners of totally infertile women? SUMMARY ANSWER: Among a sample of 26 609 partners of totally infertile women undergoing an assisted reproductive technology (ART) procedures in the whole of France over a 17-year period, there was a continuous decrease in semen concentration of about 1.9% per year and a significant decrease in the percentage with morphologically normal forms but no global trend for motility. WHAT IS KNOWN ALREADY: A global decrease in human sperm quality is still debated as geographical differences have been shown, and many criticisms have risen concerning studies with small and biased study populations or inappropriate statistical methodology. However, growing biological, toxicological, experimental and human exposure data support the endocrine disruptors' hypothesis assuming that fetal exposure to endocrine disruptors could impair reproductive outcomes. STUDY DESIGN, SIZE, DURATION: This was a retrospective and descriptive study using data registered by Fivnat, the professional association in charge of statistics for ART in France during the 1989-2005 study period. Data were provided by 126 main ART centres over the whole metropolitan territory. The source population included 154 712 men, aged 18-70, who were partners of couples undergoing their first ART cycle and for whom semen quality indicators (concentration, total motility and percentage of morphologically normal forms), measured on fresh ejaculated semen, were available. PARTICIPANTS/MATERIALS, SETTING, METHODS: The study population was 26 609 partners of women who had both tubes either absent or blocked. The temporal trends for each indicator of semen quality were modelled using a generalized additive model that allowed for nonlinear relationships between variables and were adjusted for season and age. In-depth sensitivity analyses included the reiteration of the analysis on data from a second spermiogram available for each man and on another subsample of men diagnosed as fertile. Variables such as centre, technique (standard in vitro fertilization or intra-cytoplasmic sperm injection) and an interaction factor between technique and time were also included in the model. MAIN RESULTS AND THE ROLE OF CHANCE: There was a significant and continuous decrease in sperm concentration of 32.2% [26.3-36.3] during the study period. Projections indicate that concentration for a 35-year-old man went from an average of 73.6 million/ml [69.0-78.4] in 1989 to 49.9 million/ml [43.5-54.7] in 2005. A significant, but not quantifiable, decrease in the percentage of sperm with morphologically normal forms along the 17-year period was also observed. There was no global trend but a slight, significant increase in total motility between 1994 and 1998 was observed. The results were robust after sensitivity analysis. LIMITATIONS, REASONS FOR CAUTION: Socioeconomic status could not be controlled for. Despite universal access to medical services in France, couples undergoing ART are expected to have a higher educational level on average compared with those of the general population. Therefore, the real values in the general population could be slightly lower than those presented and the decrease possibly stronger, as the population study is less likely to smoke or be overweight, two factors known to impair semen quality. WIDER IMPLICATIONS OF THE FINDINGS: As the men were selected without a priori knowledge regarding their semen quality characteristics, the results are expected to be close to the values in the general French population. The very large sample size and the robustness of the results confer great statistical power and credibility to the results. To our knowledge, it is the first study concluding a severe and general decrease in sperm concentration and morphology at the scale of a whole country over a substantial period. This constitutes a serious public health warning. The link with the environment particularly needs to be determined.
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Infertilidade Masculina/epidemiologia , Análise do Sêmen , Adulto , Idoso , Disruptores Endócrinos/toxicidade , Exposição Ambiental , França/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Dinâmica não Linear , Técnicas de Reprodução Assistida , Estudos Retrospectivos , Sêmen/efeitos dos fármacos , Contagem de Espermatozoides , Motilidade dos EspermatozoidesRESUMO
Homology-driven proteomics promises to reveal functional biology in insects with sparse genome sequence information. A proteomics study comparing plant virus transmission competent and refractive genotypes of the aphid Schizaphis graminum isolated numerous candidate proteins involved in virus transmission, but limited genome sequence information hampered their identification. The complete genome of the pea aphid, Acyrthosiphon pisum, released in 2008, enabled us to double the number of protein identifications beyond what was possible using available EST libraries and other insect sequences. This was concomitant with a dramatic increase of the number of MS and MS/MS peptide spectra matching the genome-derived protein sequence. LC-MS/MS proved to be the most robust method of peptide detection. Cross-matching spectral data to multiple EST sequences and error tolerant searching to identify amino acid substitutions enhanced the percent coverage of the Schizaphis graminum proteins. 2-D electrophoresis provided the protein pI and MW which enabled the refinement of the candidate protein selection and provided a measure of protein abundance when coupled to the spectral data. Thus, the homology-based proteomics pipeline for insects should include efforts to maximize the number of peptide matches to the protein to increase certainty in protein identification and relative protein abundance.
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Afídeos/genética , Genoma de Inseto , Proteínas de Insetos/química , Proteínas de Insetos/genética , Proteômica/métodos , Sequência de Aminoácidos , Animais , Afídeos/química , Afídeos/classificação , Afídeos/metabolismo , Bases de Dados de Proteínas , Proteínas de Insetos/metabolismo , Dados de Sequência Molecular , Análise de Sequência de Proteína , Homologia de Sequência de Aminoácidos , Espectrometria de Massas em TandemRESUMO
Arable soils are a significant source of nitric oxide (NO), a precursor of tropospheric ozone, and thereby contribute to ozone pollution. However, their actual impact on ozone formation is strongly related to their spatial and temporal emission patterns, which warrant high-resolution estimates. Here, we combined an agro-ecosystem model and geo-referenced databases to map these sources over the 12,000 km2 administrative region surrounding Paris, France, with a kilometric level resolution. The six most frequent arable crop species were simulated, with emission rates ranging from 1.4 kg N-NO ha(-1) yr(-1) to 11.1 kg N-NO ha(-1) yr(-1). The overall emission factor for fertilizer-derived NO emissions was 1.7%, while background emissions contributed half of the total NO efflux. Emissions were strongly seasonal, being highest in spring due to fertilizer inputs. They were mostly sensitive to soil type, crops' growing season and fertilizer N rates.
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Monitoramento Ambiental , Óxido Nítrico/química , Poluentes do Solo/química , Produtos Agrícolas/crescimento & desenvolvimento , França , Modelos Biológicos , Estações do Ano , Solo/análiseRESUMO
3-Hydroxy-3-methylglutaric aciduria is a rare autosomal recessive genetic disorder due to a deficiency of the 3-hydroxy-3-methylglutarylCoA lyase (HMG-CoA lyase), a mitochondrial enzyme involved in ketogenesis and in the final step of l-leucine catabolism. HMG-CoA lyase deficiency can lead, in particular circumstances, such as fever, prolonged fasting or digestive disorders, to brutal and severe hypoglycemia with metabolic acidosis and sometimes fatal coma. We report on a new case of 3-hydroxy-3-methylglutaric aciduria particular by its late onset in a 3-year-old patient. Molecular investigation identified two new sequence modifications in the HMGCL gene: c.494G>A (p.Arg165Gln) and c.820G>A (p.Gly274Arg). We remind about this case report that the therapeutical is mainly preventive and allows a very good prognosis for this disease. Long-term treatment consists in limited fasting time, continuous low protein diet and l-carnitine supplementation. Preventive measures are essential: prevention of fasting and emergency treatment during intercurrent infections.
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Erros Inatos do Metabolismo dos Aminoácidos/genética , Aberrações Cromossômicas , Genes Recessivos/genética , Hipoglicemia/genética , Meglutol/urina , Oxo-Ácido-Liases/deficiência , Oxo-Ácido-Liases/genética , Doenças Raras/diagnóstico , Doenças Raras/genética , Alelos , Erros Inatos do Metabolismo dos Aminoácidos/diagnóstico , Carnitina/administração & dosagem , Pré-Escolar , Terapia Combinada , Análise Mutacional de DNA , Dieta com Restrição de Proteínas , Éxons/genética , Humanos , Hipoglicemia/urina , Leucina/metabolismo , Masculino , Reação em Cadeia da Polimerase , Doenças Raras/terapia , Análise de Sequência de DNARESUMO
The structures of six cyclic oxazaphospholidines and three cyclic oxazaphosphinanes have been determined and their supramolecular structures have been compared. The molecules differ with respect to the functional groups attached to the central five- or six-membered rings, but have one phosphoryl group in common. The predominant feature in the supramolecular structures is the existence of relatively weak intermolecular phosphoryl XH...O=P (X = C, N) hydrogen bonds, creating in nearly all cases linear zigzag or double molecular chains. The molecular chains are in general linked to each other via very weak CH...pi or usual hydrogen-bond interactions. A survey of the Cambridge Structural Database on similar XH...O=P interactions shows a very large flexibility of the XH...O angle, which is in agreement with the DFT calculation reported elsewhere. The strength of the XH...O=P interaction can therefore be considered as relatively weak to moderately strong, and is expected to play at least a role in the formation of secondary substructures.
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Compostos Organofosforados/química , Cristalografia por Raios X , Ligação de Hidrogênio , Espectroscopia de Ressonância Magnética , Modelos Moleculares , Estrutura MolecularRESUMO
We describe a retrospective study of long-term outcome of 46 patients treated and regularly followed in France with 2-(2-nitro-4-trifluoromethylbenzoyl)-1, 3-cyclohexanedione (NTBC) for tyrosinaemia type I. Most had initial good response with normalization of liver function and metabolic parameters. Only one infant had no response to treatment and required liver transplantation. Among the 45 long-term treated patients, three underwent secondary liver transplantation: one for cirrhosis and two because of hepatocellular carcinoma. One of the latter died of transplantation complications, so that the overall survival rate was 97.5%. However, 17 of 45 showed persistent abnormal liver imaging (heterogeneous liver) and 6 had cirrhosis. Furthermore, 15 had persistently elevated levels of alpha-fetoprotein, highlighting the question of the persistent risk of carcinoma. Quality of life was usually good but compliance problems were frequent, mainly regarding the low phenylalanine-tyrosine diet. Few adverse effects were observed. A main concern was the high frequency of cognitive impairment causing schooling problems, which may be related to persistent chronic hypertyrosinaemia. In conclusion, this series confirms that NTBC treatment has clearly improved the vital prognosis and quality of life of tyrosinaemia type I patients but that many late complications persist. Long-term studies are necessary to determine whether this drug may prevent or only delay liver complications, andto survey the possible risks of the drug. A more restricted diet could be necessary to prevent the neurological impact of the disease.
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Cicloexanonas/uso terapêutico , Nitrobenzoatos/uso terapêutico , Tirosinemias/tratamento farmacológico , Pré-Escolar , Cicloexanonas/efeitos adversos , Inibidores Enzimáticos/efeitos adversos , Inibidores Enzimáticos/uso terapêutico , Seguimentos , França , Humanos , Lactente , Recém-Nascido , Fígado/fisiologia , Testes de Função Hepática , Nitrobenzoatos/efeitos adversos , Cooperação do Paciente , Estudos Retrospectivos , Fatores de Tempo , Falha de Tratamento , Tirosinemias/fisiopatologiaRESUMO
Potato virus Y (PVY, family Potyviridae, genus Potyvirus) is one of the most economically important viruses infecting potato. This plant virus is transmitted by aphids and is present in all potato growing areas across the world. Thanks to the steady set-up of biological, serological and molecular detection/characterization tools, PVY potato strain isolates have been classified in groups (PVYN, PVYO, PVYC, PVYZ and PVYE) or as sub-groups (PVYNTN and PVYN-W). Epidemiological data available for PVY show the recent modification of PVY group and sub-group proportions in PVY populations. This modification has led to the current prevalence of necrotic recombinant PVY isolates. In order to identify factors involved in this evolution of PVY populations, characterization of i) the molecular determinants of necrotic properties, ii) the impact of the increase of PVY virulence and aggressiveness on fitness, iii) the role of recombination in PVY evolution and iv) the genetic variability of viral populations have been carried out. The main results of this research have been combined with data already published to write the present review.
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McArdle's disease is a metabolic myopathy characterized by a myophosphorylase deficiency resulting in an inability to degrade glycogen stores. We report the case of a 48 years old patient who complained since adolescence of rest and exercise myalgias and presented a chronic increased plasma creatine kinase activity. First, a maximal exercise test was performed. This test demonstrated a quasi lack of rise of respiratory exchange ratio and of blood lactate, possibly due to a glycogenolytic/glycolytic pathway deficiency. Second, a biopsy of vastus lateralis muscle was performed using Bergström needle. As expected, the analysis of mitochondrial function was normal. The in vitro screening test of the glycogenolysis/glycolysis pathway showed a lack of lactate production in presence of glycogen substrate. The study of muscular metabolism of glycogen revealed a glycogen accumulation and a decrease of active and total phosphorylase activities. These data allowed us to diagnose a type V glycogenosis, or McArdle's disease. The patient appeared heterozygous for the most frequent mutation (p.R50X).
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Doença de Depósito de Glicogênio Tipo V/diagnóstico , Creatina Quinase/sangue , Teste de Esforço , Feminino , Glicogênio/metabolismo , Glicogênio Fosforilase Muscular/genética , Doença de Depósito de Glicogênio Tipo V/genética , Heterozigoto , Humanos , Ácido Láctico/sangue , Pessoa de Meia-Idade , Músculo Esquelético/metabolismo , Mutação/genética , Fosforilases/análise , Troca Gasosa PulmonarRESUMO
OBJECTIVE: The hyperimmunoglobulinaemia D and periodic fever syndrome (HIDS) was originally defined by the presence of a high serum level of immunoglobulin D associated with recurrent fever. Since the discovery of the mevalonate kinase gene (MVK) gene encoding the mevalonate kinase enzyme, most patients with a clinical diagnostic of HIDS are now found to have a mevalonate kinase deficiency based on metabolic and genetic data. We aimed to asses the value of a high IgD serum level for the diagnosis of HIDS in a cohort of patients with a phenotype of recurrent fever, and to characterize patients with a high IgD serum level without mevalonate kinase mutation. METHODS: Main clinical and biological data of 50 patients who presented with clinical signs compatible with HIDS have been prospectively registered on a standard form. Clinical data have been analysed according the IgD serum level and the presence of MVK mutation. RESULTS: The metabolic and genetic data establishing the diagnosis of HIDS correlated in all cases. In this series of 50 patients, the sensitivity of a high IgD value for the diagnosis of HIDS is 0.79. In five patients with MVK mutation, IgD levels were found to be in the normal range. Likelihood ratios indicate that IgD measurement is not relevant for the diagnostic of HIDS. Most patients with a high serum IgD level and no MVK mutation have no definite diagnosis. CONCLUSION: The clinical relevance of the IgD measurement for the diagnosis of MKD in our population appears as poor, as reflected by likelihood ratios which are both close to 1.
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Febre Familiar do Mediterrâneo/diagnóstico , Imunoglobulina D/sangue , Deficiência de Mevalonato Quinase/diagnóstico , Biomarcadores/sangue , Criança , Pré-Escolar , Febre Familiar do Mediterrâneo/genética , Feminino , Humanos , Masculino , Deficiência de Mevalonato Quinase/genética , Mutação , Fosfotransferases (Aceptor do Grupo Álcool)/deficiência , Fosfotransferases (Aceptor do Grupo Álcool)/genética , Estudos Prospectivos , Sensibilidade e EspecificidadeRESUMO
INTRODUCTION: The aim of our study was to assess the utility and reliability of magnetic resonance imaging (MRI) in antenatal diagnosis of craniosynostosis. METHODS: We retrospectively reviewed the MRI examinations of the head of 15 fetuses requested over a period of 11 years on the basis of sonographic suspicion of craniosynostosis. The postnatal diagnosis was available for 14 neonates. RESULTS: No termination of pregnancy was performed. There were four neonates with sporadic multisuture craniosynostoses, three of which were syndromic, including one Crouzon and one Pfeiffer syndrome. Eight neonates were normal, two showed cranial vault deformities without synostosis, and one was lost to follow-up. MRI showed a high predictive value for craniosynostosis, as there were no false-negative or false-positive diagnoses. However, the severity of the abnormalities were underestimated in two neonates. CONCLUSION: We suggest that prenatal MRI has diagnostic value when synostosis is suspected on ultrasonography. Moreover, MRI is accurate in the detection of associated brain abnormalities, which is an important prognostic issue in this diagnosis. Prenatal diagnosis of craniosynostosis is difficult and could benefit from three-dimensional ultrasonography and three-dimensional CT.
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Craniossinostoses/diagnóstico , Doenças Fetais/diagnóstico , Imageamento por Ressonância Magnética , Diagnóstico Pré-Natal , Feminino , Idade Gestacional , Humanos , Valor Preditivo dos Testes , Gravidez , Reprodutibilidade dos TestesRESUMO
UNLABELLED: Thyroid hormones are essential for foetus and newborn development. Preterm newborns present low levels for thyroid hormones. These low levels are related with disorder in psychomotor and neurological development. In the literature, several studies concerning newborns treated with thyroid hormone have been realized in different conditions; however, there is no consensus about preterm newborn supplementation benefit. OBJECTIVE: The aim of the study was to defined hormonal values used for normal and preterm newborns. MATERIAL AND METHODS: We reported TSH, T3T and T4L levels for 195 normal or preterm newborns, eutrophic or small for gestational age (SGA). RESULTS: A positive correlation was found between hormonal level and gestational age. This work allowed us to define a threshold for preterm newborn according to their gestational age. CONCLUSION: Owing to lack of consensus, those values are useful for clinical and biological follow-up of thyroid function for newborns at risk (SGA and preterm before 32 weeks) during the first year of life. Finally, it would be interesting to study systematic supplementation of thyroid hormone for those infants in a prospective study.
Assuntos
Recém-Nascido/sangue , Recém-Nascido Prematuro/fisiologia , Tireotropina/sangue , Tiroxina/sangue , Tri-Iodotironina/sangue , Idade Gestacional , Hospitalização/estatística & dados numéricos , Humanos , Recém-Nascido Pequeno para a Idade Gestacional/fisiologia , Valores de ReferênciaRESUMO
Small ruminant lentiviruses (SRLV) are widely spread in many countries, including Spain. However, little is known about the genetic characteristics of Spanish goat and sheep SRLV. In this study, segments from three genomic regions (pol, gag-p25 and LTR) were amplified using DNA isolated from three Spanish autochthonous sheep (one) and goats (two). Animals (one per flock) belonged to distantly located, single-species flocks (goat or sheep). Sequence analysis showed conservation of regions that are putatively relevant to viral survival. Sequences of Spanish goat and sheep SRLV were allocated into phylogenetic trees (phylograms) with known SRLV groups. The phylograms corresponding to the pol, gag-p25 and LTR regions analyzed presented a compatible topology. This showed that Spanish caprine and ovine SRLV sequences belonged to the A or D phylogenetic groups and were closer to sheep SRLV prototypes (A1 group) than to goat SRLV prototypes (B or C groups), according to the current classification [Shah, C., Boni, J., Huder, J.B., Vogt, H.R., Muhlherr, J., Zanoni, R., Miserez, R., Lutz, H., Schupbach, J., 2004a. Phylogenetic analysis and reclassification of caprine and ovine lentiviruses based on 104 new isolates: evidence for regular sheep-to-goat transmission and worldwide propagation through livestock trade. Virology 319 (1), 12-26]. It was not possible to amplify in the three genetic regions the expected fragment in additional Spanish caprine and ovine SRLV proviral DNA sequences with the PCR primers used. This suggests that there is heterogeneity at the primer binding site among Spanish SRLV sequences. It also illustrates the need to develop diagnostic tests that are sensitive in local breeds.
Assuntos
Vírus da Artrite-Encefalite Caprina/genética , Infecções por Lentivirus/epidemiologia , Vírus Visna-Maedi/genética , Visna/epidemiologia , Sequência de Aminoácidos , Animais , Produtos do Gene gag/genética , Genes pol/genética , Genoma Viral , Cabras , Dados de Sequência Molecular , Filogenia , Alinhamento de Sequência , Ovinos , Espanha/epidemiologia , Sequências Repetidas Terminais/genéticaRESUMO
Glycine encephalopathy, or nonketotic hyperglycinaemia (NKH; Mckusick 238300) is a severe autosomal recessive disease due to a defect in the glycine cleavage system (GCS), which is a complex of four subunits: P-, T-, H- and L-proteins. A P-protein (glycine decarboxylase or GLDC) deficiency was reported in about 80% of NKH patients. We performed mutation analysis of the complete coding sequence of the GLDC gene in 28 unrelated patients with neonatal NKH using denaturing high-performance liquid chromatography (DHPLC) and sequencing. Forty different gene alterations were identified, confirming the large molecular heterogeneity of the GLDC gene. Eighteen alterations were clearly disease-causing: two large deletions, four one-base deletions (c.28delC, c.1175delC, c.2186delC, c.2422delA), one 1-base insertion (c.1002_1003insT), one 4-base insertion (c.1285_1286insCAAA), one insertion/deletion (c.2153_2155delinsTCCTGGTTTA), five nonsense mutations (p.E153X, p.R236X, p.E270X, p.R337X, p.R424X) and four splice site mutations (c.861+1G > T, c.1402-1C > G, c.2316-1G > A, c.2919+1G > A). Additionally, we identified one intronic mutation outside the consensus splice sites (c.2838+5G > A) and 21 nucleotide substitutions leading to amino acid change (including three previously described mutations: p.T269M, p.R461Q, p.G771R), the pathogenicity of which should be confirmed by expression studies (p.S132W, p.Y138F, p.G171A, p.T187K, p.R212K, p.T269M, p.R373W, p.I440N, p.R461Q, p.N533Y, p.C644F, p.H651R, p.V705M, p.N732K, p.G771R, p.H775R, p.T830M, p.A841P, p.D880V, p.S957P and p.R966G). Mutation analysis allowed us to identify sequence alterations in both alleles for 19 patients and in one allele for 7 patients One patient was carrying three mutations (p.Y138F, p.T269M and p.E153X) and one patient was carrying two amino acid substitutions on the same allele (p.V705M and p.R212K) and an unidentified mutation on the other allele. No mutation could be found in two patients, suggesting possible defects in the H-protein or gene alterations that could not be identified by our technique. The potential use of genotype determination for prenatal diagnosis is emphasized.